The invention relates to a novel sulfonamidophenethanolamine having drug and bio-affecting properties. Specifically, the invention is concerned with 4'-[1-hydroxy-2-[(2-phenoxyethyl)amino]ethyl]methanesulfonanilide characterized by Formula I or a pharmaceutically acceptable acid addition or metal salt thereof, to pharmaceutical compositions containing same and to methods of producing and utilizing said sulfonamidophenethanolamine and compositions in treatment of hypertension. ##STR1##
With respect to prior art relevant to the instant invention, A. A. Larsen, et al., U.S. Pat. No. 3,341,584 patented Sept. 12, 1967, discloses an extensive series of sulfonamidophenethanolamines and teaches that such compounds are useful as adrenergic alpha-receptor blocking agents or adrenergic beta-receptor blocking agents in addition to various other pharmacological utilities. The compound 4'-[1-hydroxy-2-[ (1-phenoxyethyl)amino]ethyl]methanesulfonanilide is not, however, specifically disclosed in the Larsen, et al. patent. From a structural viewpoint, the instant compound (also referred to herein as Compound A) is homologously related to the prior art sulfonamidophenethanolamine "4-[2-(1-phenoxy-2-propylamino)-1-hydroxethyl]methanesulfonanilide." This compound, (also referred to herein as Compound B) is disclosed at column 11, Procedure 17, of the Larsen, et al. patent. According to R. H. Uloth, et al., J. Med. Chem. 9, 88-97 (1966), the aforesaid prior art compound (Compound B) is a beta-receptor blocking agent having four times the activity of dichloroisoproterenol in the isolated guinea pig tracheal spiral (see page 96, Compound 26 said reference.
Beta-adrenergic blocking agents are known to be of value in treating and controlling hypertension. They are also sometimes used in combination with an alpha-adrenergic blocking agent in preoperative management of patients with pheochromocytoma based on the rationale that beta-blockers may protect the heart from positive inotropic and chronotropic effects of high blood levels of circulating catechoamines. In the use of beta-adrenergic blocking agents in antihypertensive therapy, reduction of blood pressure is often accompanied by pronounced bradycardia (i.e. reduced heart rate). This is considered a serious side effect in that it generally contributes to exercise intolerance.
In the case of the aforesaid prior art sulfonamidophenethanolamine (Compound B) of U.S. Pat. No. 3,341,584, a substantial decrease in heart rate of mammals is elicited at effective antihypertensive or hypotensive doses whereas, surprisingly at effective antihypertensive or hypotensive doses, the compound of the instant invention elicits little or no significant change in heart rate.